Intramembrane receptor-receptor interactions: integration of signal transduction pathways in the nervous system

During recent years a large number of observations have been made indicating that neuropeptides and other transmitters in various brain areas can regulate the affinity of monoamine receptors via the activation of their own receptors. These "receptor--receptor interactions" can either take place at the plasma membrane level or use intracytoplasmatic loops. This review is mainly focused on the evidence for hetero-regulation of dopamine (DA) D2 receptors in the basal ganglia. The existence of such receptor--receptor interactions increases the plasticity of transmission and opens up the possibility of developing new drugs which indirectly modulate receptor recognition and decoding processes. This would avoid the use of direct receptor agonists or antagonists which induce major side effects such as tolerance and abstinence. Disturbances in the receptor--receptor interactions, including DA D2 receptors, may be involved in the development of neurological and mental diseases such as schizophrenia.